All publications and patent applications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
Rheumatism refers to any of several pathological conditions of the muscles, tendons, joints, bones, or nerves, characterized by discomfort and disability. It is estimated that over 100 rheumatic diseases affect the joints and other connective tissues of animals.
Arthritis generally refers to the inflammation of a joint or joints which results in pain and swelling. The two most common forms of arthritis are osteoarthritis and rheumatoid arthritis. Osteoarthritis is characterized by chronic degeneration of the cartilage of the joints, mainly in older persons. Rheumatoid arthritis, sometimes called arthritis deformans, is a chronic and progressive systemic disease, especially common in women, characterized by stiffness, swelling and inflammation of the joints and sometimes leading to deformity and permanent disability. Sufferers of rheumatoid arthritis may also have general symptoms of fatigue, weakness, and loss of appetite. While there is no cure, these diseases can sometimes be managed by lifestyle and diet changes.
Many other diseases also cause pain, inflammation and fevers. Rheumatic fever is an acute inflammatory disease occurring during recovery from infection with group A streptococci, having an onset marked by fever and joint pain. It is associated with polyarthritis, Sydenham's chorea, and endocarditis, and is frequently followed by scarring of the heart valves. Lupus erythematosus, also known as systemic lupus erythematosus, is a chronic disease of unknown origin characterized by red, scaly lesions or patches on the face and upper portion of the trunk. Erythema nodosum is a skin disease associated with joint pain, fever, hypersensitivity, or infection, and characterized by small, painful, pink to blue nodules under the skin and on the shins that tend to recur. Gout is an inherited disorder of uric-acid metabolism occurring predominantly in men, characterized by painful inflammation of the joints, especially of the feet and hands, and arthritic attacks resulting from elevated levels of uric acid in the blood and the deposition of urate crystals around the joints. The condition can become chronic and result in deformity.
When diet and lifestyle changes are not sufficient to alleviate the symptoms of rheumatism and rheumatoid-like diseases, pharmaceuticals are often used for relief from the resultant pain, discomfort, and fever. The antiinflammatory, analgesic and antipyretic agents and drugs often employed for this purpose are a heterogeneous group of compounds; often chemically unrelated, which nevertheless share certain therapeutic actions and side effects. For a comprehensive discussion of such drags see Insel, P. A., Analgesic-Antipyretic and Antiinflammatory Agents and Drugs Employed in the Treatment of Gout, In Goodman & Gilman's The Pharmacological Basis of Therapeutics, Ninth Edition, Chapter 27 (1996).
Herbal Medicines
It is estimated that approximately 50 percent of the thousands of drugs commonly used and prescribed today are either derived from a plant source or contain chemical imitations of a plant compound (Mindell, E. R., Earl Mindell's Herb Bible, A Fireside Book (1992)). Currently, a number of medicinal formulations contain herbal components or extracts from herbs. Technically speaking an herb is a small, non-woody (i.e., fleshy stemmed), annual or perennial seed-bearing plant in which all the aerial parts die back at the end of each growing season. As the word is more generally used and as it is used herein, an herb is any plant or plant part which has a medicinal use. Thus, the term herb is also generally used to refer to the seeds, leaves, stems, flowers, roots, berries, bark, or any other plant parts that are used for healing.
Herbal medicines have been used for treating various diseases of humans and animals in many different countries for a very long period of time (see, e.g., Kessler et al., The Doctor's Complete Guide to Healing Medicines, Berkley Health/Reference Books (1996); Mindell, supra). Herbal medications are available in many forms, including capsules, tablets, or coated tablets; pellets; extracts or tinctures; powders; fresh or dried plants or plant parts; prepared teas; juices; creams and ointments; essential oils; or, as combinations of any of these forms. Herbal medicines are administered by any one of various methods, including orally, rectally, parenterally, enterally, transdermally, intravenously, via feeding tubes, and topically.
The bark of the willow tree has been used to treat fever since the mid-eighteenth century in England. The active ingredient in willow bark is a bitter glycoside called salicin, which on hydrolysis yields glucose and salicylic alcohol. Aspirin (acetylsalicylic acid) and aspirin-like drugs (e.g., ibuprofen), all of which are often called nonsteroidal antiinflammatory drugs (NSAIDs), are frequently used to treat pain, fever, and inflammation. Meadowsweet is another herb that contains salicylates. Treatment of arthritic and arthritic-like symptoms with willow bark or meadowsweet requires the consumption of prohibitively large quantities of herbal teas made from these plants. The entire Populus species (i.e., poplar trees and shrubs) also contains salicylate precursors and poplar-buds have been used in antiinflammatory, antipyretic and analgesic medications.
While preliminary evidence suggests that joint inflammation may be reduced by the intake of plants which contain gamma-linolenic acid (e.g., black currant, borage, evening primrose), relief using these plants also requires the intake of large amounts of plant material. The alkaloid colchicine is extracted from the corm and the seeds of autumn crocus (Colchicum autumnale) and used in either tablet form or intravenously for patients with gout. Colchicine is also used to treat familial Mediterranean fever. However, as little as 7 mg of colchicine has been found to be fatal, although the normal fatal dose is 65 mg. European goldenrod (Solidago virgaurea) has been used to treat arthritis, kidney inflammation, and as a headache remedy for treating flu, sore throat, malaria and measles. Modern research has found that licorice (Glycyrrhiza glabra), which contains a medically active terpene component, can reduce arthritic activity. However, the cortisone-like component of the saponin like glycoside glycyrrhizin causes dangerous side effects, including abnormal heart action and kidney failure, triggered by potassium depletion. While alfalfa, black cohosh, blue-green algae, bog bean, burdock root, celery seeds, chaparral, comfrey, dandelion, devil's claw, feverfew, fresh ginger, juniper, mustard, parsley, sassafras, valerian, wormwood and yucca have all been reputed to bring relief of arthritis, there is little or no scientific evidence to support such assertions. For a more complete discussion of herbal-based medicines see Mindell, supra; Culpeper's Complete Herbal, W. Foulsham & Co., Ltd. (originally published in the mid 1600's); and, Rodale's Illustrated Encyclopedia of Herbs, Rodale Press (1987).
U.S. Patents have been issued for herbal medicinals used for the treatment of various diseases and other health-related problems afflicting humans and animals. For example, U.S. Pat. No. 5,417,979 discloses a composition comprising a mixture of herbs, including species of Stephania and Glycyrrhiza, as well as their extracts, which is used as an appetite stimulant and for the treatment of pain. Herbal compositions which include Glycyrrhiza uralensis have been found useful for treating eczema, psoriasis, pruritis and inflammatory reactions of the skin (U.S. Pat. No. 5,466,452). U.S. Pat. No. 5,595,743 discloses various herbal compositions which include licorice extract (Glycyrrhiza) and siegesbeckia, sophora, stemona and tetrandra herbs used for the treatment of various mammalian diseases, including inflammation and rheumatoid arthritis. Ocular inflammation can be treated with a pharmaceutical composition containing the plant alkaloid tetrandrine (U.S. Pat. No. 5,627,195). U.S. Pat. No. 5,683,697 discloses a pharmaceutical composition having anti-inflammatory, anti-fever, expectorant or anti-tussive action, wherein the composition includes plant parts from the species Melia, Angepica, Dendrobium, Impatiens, Citrus, Loranthus, Celosia, Cynanchum and Glehnia. An herbal formulation comprising extracts of the roots, rhizomes, and/or vegetation of Alphinia, Smilax, Tinospora, Tribulus, Withania and Zingiber has been found to reduce or alleviate the symptoms associated with rheumatoid arthritis, osteoarthritis, reactive arthritis and for reducing the production of proinflammatory cytokines (U.S. Pat. No. 5,683,698).
Based on the foregoing, there currently exists a need for antiinflammatory, analgesic and antipyretic herbal-based therapeutics which have low toxicity and few side effects. For example, there is a need for non-aspirin therapeutics for the treatment of fever, pain and inflammation associated with rheumatoid arthritis and osteoarthritis. The novel compositions of the present invention fulfill those requirements.